Innate Lymphocytes-L13

Question 1

People lacking NK cells are susceptible to what types of illness?

Answer 1

-Herpetic viruses

Question 2

Two subsets of NK cells in humans

Answer 2

CD56 CD3- (dim and bright)

Question 3

What attracts NK cells to the tissue from the circulation

Answer 3

-Chemoattractants–interferons

Question 4

Safety features of NK cells

Answer 4

• Can only kill one target cell at a time and at a certain distance
• Sum of interactions between inhibitory receptors and activating receptors determines the decision to kill or not to kill
• Default is to remain inhibited
• NK cells are activated locally

Question 5

Macrophage recruitment of NK cells

Answer 5

• Inflammatory cytokines recruit and stimulate NK cells
• NK cell and macrophage form a conjugate pair where IL12 and IL15 activate the NK cell
• NK cells proliferate and turn into effector NK cells secreting IFNy
• IFNy binds macrophages and activates them
• It’s a cycle

Question 6

NK cell activation by dendritic cells

Answer 6

• IL15 activates
• When innate immunity has infection under control NK cells will limit DC
• Otherwise NK cells will promote DC differentiation and their migration to the lymph node to get the adaptive immune response going

Question 7

NK cells express what special kinds of receptors?

Answer 7

• Toll like receptors: TLRs

- TLR 3,7,8

Question 8

-TLR3

Answer 8

-Expressed by NK cells for dsRNA (viral)

Question 9

TLR 7,8

Answer 9

-Expressed by NK cells for ssRNA

Question 10

What senses MHC class 1 in NK cells for an inhibitory signal?

Answer 10

• KIR molecules

- CD94:NKG2A complexes

Question 11

Nk cell effector function

Answer 11

• Selectively kill target cells in distress that down-regulate MHC class 1 molecules, or upregulate stress-induced self molecules
• Sums the inputs to decide if it needs to inhibit or activate

Question 12

Activation of NK cells requirements

Answer 12

• Two signals from two or more activating receptors
• NKG2D is a common activating signal
• In the presence of IgG the Fc receptor can activate NK cells without help from another receptor

Question 13

NKG2D

Answer 13

-Activating signal for NK cells

Question 14

NK cell detection of self (the first detection)

Answer 14

• Via CD94: NKG2A receptor complex that detects the presence of MHC class 1 (HLA) based on HLA-E presentation of leader peptides from HLA-A, B, C
• Get turned on before KIRs in development
• Sends inhibitory signal

Question 15

KIR

Answer 15

• Killer inhibitory receptors
• Another way for NK cells to detect self
• Direct recognition of HLA-A,B, C. No peptide recognition involved.
• Predominant self receptor after education

Question 16

Education of NK cells

Answer 16

• A threshold of inhibitory signaling that NK activating receptors must overcome
• Basically setting a threshold of signals for activation
• Tells us how much Vav activation necessary to make NK cell active

Question 17

NK cells in the control of CMV

Answer 17

• CMV will down regulate class 1 MHC and interferes with peptide presentation by HLA to avoid CD8 T cell response.
• BUT this makes them vulnerable to NK killing
• CD94:NKG2C is an activating complex
• This subset of NK cells expressing this complex expands and stays elevated throughout life (NK memory)

Question 18

Uterine NK cells

Answer 18

• Control invasion of fetal trophoblast cells in the developing placenta
• Make angiogenic factors that promote vessel growth
• KIR2DL4:HLA-G interaction

Question 19

Gamma delta T cells

Answer 19

• Plentiful in tissues, particularly in the gut
• Not a ton circulating in the blood
• Tissue homeostasis, surveillance, and repair
• Not MHC restricted

Question 20

Vgamma9:Vdelta 2 T cells

Answer 20

• Recognize phosphoantigens presented on cell surfaces by CD277
• Promote inflammation that will lead the control of the infection

Question 21

Vgamma4:Vdelta5 T cells

Answer 21

• Respond to CMV infected cells
• Upregulate EPCR which binds phospholipids
• Mediates inflammatory cytokine production

Question 22

Vgamma:Vdelta1 T cells

Answer 22

-Recognize lipid antigens presented by CD1d

Question 23

CD1s

Answer 23

Present mycobacterial lipids to gamma delta T cells which is important for control of leprosy and TB

Question 24

NKT cells

Answer 24

• Express NK receptors like NKG2D
• Require signal from TCR and from a cytokine for activation
• Initiate inflammation

Question 25

MAIT cells

Answer 25

• Mucosa associated invariant T cells
• Effector alpha:beta T cells that live in the mucosa
• Bind to heterocyclic molecules made during riboflavin synthesis
• Detects YEAST and BACTERIA